Characteristic chromosomal abnormalities are associated with specific histological subtypes of non-Hodgkin lymphoma (NHL). The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in NHL, occurring in 70%-90% of cases of follicular lymphoma, 20%-30% of diffuse large B-cell lymphoma, and 5%-10% of other less common subtypes. The t(14;18)-positive NHL may represent a homogenous group and, consequently, increase etiologic specificity in epidemiological studies. Although the t(14;18) has important clinical ramifications, its etiologic significance remains to be determined. Two population-based, case-control studies addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. Both studies found that the association between pesticide exposures and risk of NHL was largely limited to t(14;18)-positive NHL cases. However, the findings regarding cigarette smoking, family history of hematopoietic cancer, and hair dye use were not entirely consistent. These results indicate that defining subgroups of NHL according to t(14;18) status may be useful for etiologic research, particularly for exposures that are genotoxic or may contribute to the development of NHL through pathways involving the t(14;18). Studies to further evaluate these associations and delineate the effects of various exposures in other genetically defined subgroups of NHL are warranted.